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EC number: 611-056-6 | CAS number: 538313-26-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
According to these criteria, applying the CLP regulation N°1272/2008/EC and considering the ambiguous results of the present 442 B study, the tested substance CuDABT should be classified as sensitizer category 1B.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vitro
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 11 may to 24 may 2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 442B (Skin Sensitization: Local Lymph Node Assay: BrdU-ELISA)
- Version / remarks:
- adopted 22 July 2010
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA): BrdU-ELISA
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Provider : AUTOLIV ASP, 16700 W. Hwy 83, Promontory, UTAH 84307, USA
- batch No. P3656461
- Expiration date of the lot/batch: august 25th 2020
- Purity: 97.4%
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in a restricted area dedicated to explosive products, at outside temperature and humidity
- Solubility and stability of the test substance in the solvent/vehicle: not soluble in water
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: no treatment
FORM AS APPLIED IN THE TEST (if different from that of starting material)
homogeneous suspensions in dimethyl formamide (DMF) - Species:
- mouse
- Strain:
- CBA:J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Elevage Janvier LABS
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known:
- Age at study initiation: 9 weeks
- Weight at study initiation: 20-25 g
- Housing: individually in suspended solid-floor polypropylene cages furnished with softwood woodflakes.
- Diet ad libitum
- Water ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 10 per hour
- Photoperiod (hrs dark / hrs light): 12h/12h
- IN-LIFE DATES: From: To:11 May to 24 May 2016 - Vehicle:
- dimethylformamide
- Concentration:
- test item diluted in DMF at 50%, 25% and 10%
- No. of animals per dose:
- 4 females
- Details on study design:
- - Compound solubility: test item is not soluble in water or other vehicle tested. However, a homogeneous blue suspension was obtained with 10% and 50% of dimethyl formamide (DMF). 25% of DMF was chosen as vehicle.
PRELIMINARY SCREENING TEST
preliminary test was performed using one mouse treated daily (days 1,2 and 3) with a diluted test item at 50% in DMF
no mortality and no signs of systemic toxicity were noted
no cutaneous reaction (erythema) was noted at the tested concentration of 50%
the percent in ear thickness increase was 9.1% on day 3 versus day 1 and 14.3% on day 6 versus day 1
therefore, 50% was chosen as the highest concentration for the main test
MAIN STUDY
TREATMENT PREPARATION AND ADMINISTRATION:
3 groups of female mice were treated for 3 consecutive days with 50 µL (25µL per ear) of the test item diluted at concentrations of 50%, 25% and 10% in dimethylformamide (DMF). A vehicle group of 4 mice was treated with DMF. On day 5, 0.5mL of BrdU solution (10 mg/mL) mas injected by the intraperitoneal route. On day 6, the proliferation of lymphocytes in the draining auricular lymph nodes was determined by measurement of BrdU content in DNA of lymphocytes using an ELISA kit. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- no statistics
- Positive control results:
- BrdU index (mean): 1.630, stimulation index SI: 1.92 +/- 0.36.
- Key result
- Parameter:
- SI
- Value:
- 2.44
- Variability:
- 0.43
- Test group / Remarks:
- test item 10%
- Key result
- Parameter:
- SI
- Value:
- 1.88
- Variability:
- 0.26
- Test group / Remarks:
- test item 25%
- Key result
- Parameter:
- SI
- Value:
- 1.62
- Variability:
- 0.1
- Test group / Remarks:
- test item 50%
- Cellular proliferation data / Observations:
- DETAILS ON STIMULATION INDEX CALCULATION: according to O.E.C.D. guideline No.442-B, the result obtained here is borderline positive results as Stimulation Index (SI) values between 1.6 and 1.9 have been obtained (considering the average and deviation).
The maximum SI value, registered at the lowest dose, may be explained by a best bioavailability of the test item. Indeed at all concentrations, the preparations were a blue suspensions and despite a vigorous homogenisation before each treatment, a sedimentation was noted which confirm that tested concentration are aboce the solubility limit. This sedimentation was higher in the group treated at the highest concentration of 50%.
EC1.6 CALCULATION: can not be determined as all SI values were higher than 1.6 (borderline positive)
CLINICAL OBSERVATIONS: no mortality and no signs of systemic toxicity, no erythmae were noted in the test and control animal during the test
BODY WEIGHTS: bodyweight changes of the test animals between day 1 and day 6 were comparable to those observed in the corresponding control group animals over the same period and are not consodered as relevant. - Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- According to the criteria, applying the CLP regulation N°1272/2008/EC and considering the ambiguous results of the present 442 B study, the tested substance CuDABT should be classified as sensitizer category 1B (also see Sensitisation Summary for more details). The signal word "warning" and the hazard statemnt H317 "may cause an allergic skin reaction" are required.
- Executive summary:
The test item was performed to assess the skin sensitisation potential of the test item Copper Dianmmine Bitetrazole (CuDABT) in the CBA/J strain mouse following topical applications to the dorsal surface of the ear. The basic principle underlying the LLNA:BrdU is that sensitizers induce proliferation of lymphocytes in the lymph nodes drainning the site of the test item application. The experimental protocol was established according to the O.E.C.D. Guideline No.442 -B adopted 22 July 2010.
3 groups of female mice were treated for 3 consecutive days with 50 µL (25µL per ear) of the test item diluted at concentrations of 50%, 25% and 10% in dimethylformamide (DMF). A vehicle group of 4 mice was treated with DMF. On day 5, 0.5mL of BrdU solution (10 mg/mL) mas injected by the intraperitoneal route. On day 6, the proliferation of lymphocytes in the draining auricular lymph nodes was determined by measurement of BrdU content in DNA of lymphocytes using an ELISA kit.
No mortality and no signs of systemic toxicity were noted in the test and control animals during the test.
The percent in ear thickness increase was -3.4 +/-7.1, -2.4 +/-6.1, 5.3 +/-10.8 on day 6 versus day 1, in mice treated with test item at 10%, 25% and 50%. The percent in ear weight increase was 7.5%, 7.3%, 5.5% on day 6 in mice treated with test item at 10%, 25%, 50%. No cutaneous (erythema) was noted. The test item has to be considered as not excessively irritant at these concentrations in accordance with the O.E.C.D. criteria.
The Stimulation Index (SI) calculated by individual approach was 2.44 +/-0.43, 1.88 +/-0.26, 1.62 +/-0.10 for treated groups at 10%, 25%, 50%. which is ambiguous according to the 442B OEDC guideline. The maximum SI value, registered at the lowest dose, may be explained by a best bioavailability of the test item. Indeed at all concentrations, the preparations were a blue suspensions and despite a vigorous homogenisation before each treatment, a sedimentation was noted, which means that the tested solution was above the solubility limit. This sedimentation was higher in the group treated at the highest concentration of 50%.
The results obtained in these experimental conditions, enable to conclude that the test item Copper Diammine Bitetrazole (CuDABT) has to be classified as a sensitiser in Category 1B, in accordance with the Regulation EC No. 1272/2008.
Referenceopen allclose all
Local irritation: test item has to be considered as not excessively irritant at these concentrations
test item | ear weight increase on day 6 | ear thickness increase on day 3 versus day1 | ear thickness increase on day 6 versus day 1 | cutaneous reaction |
10% | 7.5% | 5.0 +/-5.8 | -3.4 +/-7.1 | no |
25% | 7.3% | 3.6 +/-4.6 | -2.4 +/-6.1 | no |
50% | 5.5% | 7.5 +/-3.2 | 5.3 +/-10.8 | no |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
According to guidance R7a. and by definition, a skin sensitiser is an agent that will lead to an allergic response in susceptible individuals following skin contact. As a consequence of a secondary - usually organ-specific - subsequent re-exposure, adverse health effects on the skin (allergic contact dermatitis).
An OECD 442B test has been conducted according to annex VII to assess any sensitizer properties of CuDABT.
No mortality and no signs of systemic toxicity were noted in both the CuDABT and control animals during the test. No cutaneous erythema was noted. The Stimulation Index (SI) calculated by individual approach was 2.44 +/-0.43, 1.88 +/-0.26, 1.62 +/-0.10 for treated groups at 10%, 25% , 50%. The EC 1.6 could not be determined as all SI values were higher than 1.6.
As per OECD guidance: “For a borderline positive response between an SI of 1.6 and 1.9, (which is the case here), users may want to consider additional information such as dose-response relationship, evidence of systemic toxicity or excessive irritation, and where appropriate, statistical significance together with SI values to confirm that such results are positive (10). Consideration should also be given to various properties of the test substance, including whether it has a structural relationship to known skin sensitizers, whether it causes excessive skin irritation in the mouse, and the nature of the dose-response observed. These and other considerations are discussed in detail elsewhere”
In this present study the dose-response is not usable, in part because of the very poor solubility of the test substance. There is no dose-response curve which confirms the dose-effect relationship in the present study.
Considering that the low solubility of the substance may interfere with the accuracy of the test, other parameters have to be considered to confirm if the borderline result should be considered as positive or negative:
• Evidence of systemic toxicity: there is no evidence of systemic toxicity
• Excessive irritation: there are no signs of irritation in the study
OECD also states: “Collecting data at the level of the individual mouse will enable a statistical analysis for presence and degree of dose-response relationship in the data. Any statistical assessment could include an evaluation of the dose-response relationship as well as suitably adjusted comparisons of test groups (e.g. pair-wise dosed group versus concurrent solvent/vehicle control comparisons).”
There is no data in the study that justifies the dose-response relationship and as a consequence no dose-response based findings are available to justify a positive response.
According to the Guidance R7a., substances shall be classified as skin sensitisers (Category 1) where data are not sufficient for sub-categorisation in accordance with the following criteria:
(a) if there is evidence in humans that the substance can lead to sensitisation by skin contact in a substantial number of persons; or
(b) if there are positive results from an appropriate animal test (see specific criteria in paragraph 3.4.2.2.4.1).
According to these criteria, applying the CLP regulation N°1272/2008/EC and considering the ambiguous results of the present 442 B study, the tested substance CuDABT should be classified as sensitizer category 1B.
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